MK-801和L-NA对成年仓鼠视网膜节细胞轴突损伤后存活与再生的影响

目的 研究NMDA受体阻断剂MK-801和一氧化氮合酶抑制剂L-NA对成年仓鼠视网膜节细胞(下称节细胞)轴突切断后存活和再生的影响。方法 切断动物左侧视神经后分两组：存活组存活2、7或14d;再生组视神经眶侧断端同一段坐骨神经吻合后存活28d。所有实验动物自视神经切断前1d开始,每日接受腹腔注射MK-801和／或LNA直至处死。结果存活节细胞均数在MK-801组与对照组间无显著性差异,但L-NA组在术后2和7d节细胞数较对照组显著增加,合用MK-801／LNA较单用MK-801或L-NA使更多节细胞存活。而MK-801或L-NA对节细胞轴突在周围神经移植物内的再生均无明显作用。结论 lmg／kg剂量的MK-801对节细胞的存活无明显作用,但同时阻断NMDA受体和抑制一氧化氮合酶比单纯抑制一氧化氮合酶对节细胞有更强的神经保护作用。1．0mg／kgMK-801或4．5mg／kgL-NA对节细胞轴突的再生无明显促进作用。

EFFECTS OF MK-801 AND L-NA ON THE SURVIVAL AND REGENERATION OF AXOTOMIZED RETINAL GANGLION CELLS IN ADULT HAMSTERS

Objective The present study examined the effects of MK-801,an antagonist against NMDA receptor,and L-NA,an inhibitor of nitric oxide synthase,on the survival and regeneration of axotomized retinal ganglion cells(RGCs) in adult hamsters. Methods This study consisted of two groups.The animals in the survival group survived for 2,7,or 14 days after their left optic nerves(ON) were transected intraorbitally.Animals in the regeneration group survived for 28 days after receiving the left ON transection and peripheral nerve transplantation onto the ocular ON stump.All the experimental animals were treated with daily intraperitoneal injections of MK-801 and/or L-NA one day before ON transection till they were killed. Results No significant difference in the number of surviving RGCs was found between the MK-801-treated and control animals.However,L-NA promoted more RGCs to survive at 2 and 7 day postoperatively when compared with the control animals.More RGCs were detected in animals receiving combined treatment of MK-801/L-NA in comparison to those treated with MK-801 or L-NA only.Similar numbers of regenerating RGCs were encountered among the animals receiving MK-801,L-NA or saline.Conclusion 1^0mg/kg of MK-801 has no promoting effects on the survival of axotomized RGCs,whereas stronger neuroprotective effects can be harvested with combined blockade of NMDA receptor and inhibition of nitric oxide synthesis than with MK-801 or L-NA only. Neither 1^0mg/kg of MK-801 nor 4^5mg/kg of L-NA could enhance the axonal regeneration of axotomized RGCs into a peripheral nerve graft.